After a man infected with the Cordilla virus escaped quarantine, and the virus broke out into the main population of Los Angeles, the Secret Service felt it was no longer safe for President Palmer to remain in the city. The Secret Service, under the authorization from Special Agent in Charge Kurtzman and Assistant Special Agent in Charge Aaron Pierce, invoked "Section 32" which effectively ordered Palmer to leave with the agents. Taking Aaron aside, Palmer was able to persuade Pierce to allow him to stay in the city until the crisis was resolved.

Agent Davis and various other Secret Service agents were placed in charge of protecting Secretary of Defense James Heller and Audrey Raines were ambushed by terrorists; five agents were shot and killed, and one was seriously wounded as Heller and Raines were captured. Agents Greg Merfield and Frank Wells, following orders directly from President Charles Logan, tried to arrest Jack Bauer in the middle of a sensitive CTU operation. Their intereference gave the terrorist mastermind Habib Marwan the chance to escape from The Hub. Later, the corrupt agent Dale Spalding attempted to murder Bauer for Walt Cummings. He believed he was successful.

Aaron Pierce was the Special Agent in Charge of President Charles Logan's protective detail after serving under the administrations of David Palmer and John Keeler. When First Lady Martha Logan realized Charles was planning to send her back to a mental institution in Vermont, she attempted to run away, and the Secret Service was tasked with finding her. Aaron eventually found her hiding in the horse stable of the Presidential Retreat, and despite Martha's insistence that someone in her husband's administration was undermining the President's authority, Agent Pierce had to let the other agents take her back. When Jack Bauer met with Mike Novick to try and expose Walt Cummings as a co-conspirator with terrorists, Cummings ordered the Secret Service to arrest Bauer. Jack was, however, able to convince Pierce to let him confront Cummings, and after his confession, the Secret Service remanded Walt into custody. During the terrorist's ambush of the Suvarov's motorcade, six Secret Service agents were killed; Agent Pierce was able to take down the remaining assassins. That night, after Jack's discovery of President Logan's involvement with the terrorist attacks, Agent Justin Adams was ordered to kill Aaron, but Martha was able to kill Adams, saving Agent Pierce. As evidence was provided to the Attorney General against President Logan, the Secret Service and an agent of the U.S. Marshals arrested Logan for treason.

Agents Brian Gedge and Edward Vossler, who were moles under the payroll of Colonel Ike Dubaku, both sought to impede First Gentleman Henry Taylor's private investigation into Rodger's death, as Henry was unwilling to accept that his son committed suicide. Agent Gedge attempted to convince Ethan Kanin that Mr. Taylor was on a wild goose chase and was "concerned about his mental state." When Roger's ex-fiancé, Samantha Roth, tried to give information to the First Gentleman, Agent Gedge murdered Samantha and attempted to kill Henry as well. While Mr. Taylor managed to kill Agent Gedge, he was immediately re-captured by Agent Vossler, who turned him over to Dubaku as a hostage. Agent Vossler was later killed by Jack Bauer while being interrogated to find the First Gentleman's whereabouts.

During General Benjamin Juma's assault on the White House, several Secret Service agents were killed by Juma and his commandos. As FBI agent Larry Moss informed Bill Buchanan about the assault, the Secret Service was able to get President Allison Taylor to the lock down with the help of Jack Bauer, but not before Juma blocked word from getting out that the President was secure. Additional Secret Service agents, under the lead of Special Agent in Charge Ted Hovis began to engage Juma's men in the hallways. Accessing the Secret Service communications channel, Juma bluffed Hovis into backing down, claiming to kill President Taylor if he did not comply. After Bill Buchanan sacrificed himself by taking out some of Juma's men, the Secret Service Emergency Response Team in conjunction with the FBI's Hostage Rescue Team retook the White House from the commandos.

Agent Aaron Pierce was responsible for protecting First Daughter Olivia Taylor during the assault on the White House, and was asked by her to head up her protective detail afterwards. Upon discovering Olivia's involvement with the assassination of Jonas Hodges, Agent Pierce with the help of Ethan Kanin, gathered evidence against her, and upon the President's orders, remanded her into federal custody.

President of the IRK Omar Hassan and his family were evacuated from the United Nations Headquarters to McGuire Air Force Base by a team of seven Secret Service agents under the charge of Agent Molly O'Connor, as well as Jack Bauer and Renee Walker by request of President Allison Taylor. A group of Black Ops commandos under orders from General David Brucker assaulted the security detail, attempting to capture Hassan. While Jack and Renee retreated with Hassan and his family, the remaining Secret Service agents, and Agent O'Conner in particular, provided cover fire to give them time to escape. Upon the discovery of Brucker and Rob Weiss's attempt to subvert President Taylor's refusal to comply with the terrorist demands, the Secret Service arrested the two men for treason. Later, Jack Bauer non-lethally shot three Secret Service agents to capture former President Charles Logan because of his involvement with Renee's murder.

Although the Secret Service is most known for its protective duties, it is primarily responsible for investigating violations of federal laws relating to counterfeiting and other financial crimes of the United States. This is due in part because prior to the September 11th attacks, the Secret Service was under the jurisdiction of the Department of the Treasury. It started presidential protection duties after the assassination of William McKinley in 1901. After the assassination of Robert Kennedy in 1968, the Service's mandate was altered further to include protection of presidential candidates.